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ISSN 2320-5407

International Journal of Advanced Research (2016), Volume 4, Issue 7, 859-864

Journal homepage:http://www.journalijar.com
Journal DOI:10.21474/IJAR01

INTERNATIONAL JOURNAL
OF ADVANCED RESEARCH

RESEARCH ARTICLE
PLASMAPHERESIS: AN EXPERIENCE AT A TERTIARY CARE HOSPITAL.
Sajad Geelani, Mudasir Qadri, Yasir Bashir, Hilal Bhat, Nadeem Shoukat, Nusrat Bashir, Fahim Manzoor,
Shuaeb Bhat, Javid Rasool and Aleem Jan.

Manuscript Info

Abstract

Manuscript History:

Objectives:- To analyze our experience with 105 cases who underwent


plasmapheresis for various disorders.
Materials and Methods:-Retrospective review of Plasmapheresis(PE) was
done over a period of 13 years, from july 2015 to August 2002 in a tertiary
care centre.
Results:- The main indication for PE was GuillainBarresyndrome( GBS) (
31%) . Age of patients ranged from 18-62
years. The most common
complications were paraesthesias and/or cramps (36.1%) and hypocalcemia
(7%).There was no mortality related to the procedure.
Conclusion:-The analysis of 105 cases of plasmapheresis in our department
showed that the procedure is safe, with only minimal procedure related
complications and no mortality.

Received: 12 May 2016


Final Accepted: 26 June 2016
Published Online: July 2016

Key words:
Plasmapheresis,Therapeutic plasma
exchange,Guillan Bare syndrome..

*Corresponding Author
Nusrat Bashir.

Copy Right, IJAR, 2016,. All rights reserved.

Introduction:-

The word apheresis is derived from the Greek word aphaeresis which means to separate take away by force or
to remove. The term was originally used by Abel, Rowntree and turner to describe manual plasma exchange, the
removal of units of whole blood anticoagulated with heparin followed by centrifugation to separate the blood in to
cellular elements and plasma (1). The cellular elements were then mixed with a replacement for the discarded
plasma and reinfused.
In common usage, the terms plasma exchange and plasmapheresis are used interchangeably, although the two
procedures are different. Plasmapheresis removes a small amount of plasma, usually less than 15 % of the patients
blood volume, and therefore does not require replacement of removed plasma. The most common pharesis
procedures performed in the United States are those in which plasma is collected from the healthy donors for
transfusion or manufacture in to products such as albumin, IV Ig, factor concentrates, and laboratory reagents.
TPE, through the bulk removal and replacement of plasma, removes pathological substances such as pathological
antibodies, immune complexes and cytokines. It has been presumed that the removal of these substances represents
the major mechanism of action of TPE. However, this mechanism does not explain the length of response seen in
some disorders. Additional evidence that TPE may have immunomodulatory effect beyond the removal of
immunoglobulins. Reported effects of TPE on immune function include T-cell modulation with a shift from in the
Th1/Th2 balance with a shift towards Th2, suppression of IL-2 and IFN- production (2,3), and in vitro cultures
demonstrating in concanavalin A-induced suppressor functions . (4)
Devices used to perform TPE can be divided in to two broad categories, those that separate the plasma from the
cellular components based on size and those that separate components based on density. TPE-utilizing filters are not
widely used in the United States. (5). It is important to realize that there is some mixing that occurs at the interface
between the layers in the centrifuge. The implication of this is that some platelets may be present in the plasma layer
and, depending upon several factors, there may be a resulting loss of platelets during TPE. (5)

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International Journal of Advanced Research (2016), Volume 4, Issue 7, 859-864

Because of the dilution of the plasma by the replacement fluid, the substance of interest can not be completely
removed from the circulation. For each 1-1.5 plasma volume exchanged, approximately 60-70% of the substance
present in the plasma at the start of the plasma volume will be removed. As additional volumes are exchanged, the
absolute amount removed becomes lower, although removal of a fixed 60-70% still occurs. (6). Treating volumes
beyond 1.5 plasma volumes removes smaller, less clinically important amounts of pathological substances present in
the plasma while prolonging the procedure and exposing the patient to more replacement fluid and anticoagulant.
The result is increasing risk of complications without increasing benefit to the patient. There are diminishing returns
in treating beyond 1.5 plasma volumes.
The procedure is non selective, removing both normal and pathological plasma components. Significant declines in
factor V (FV), FVII, FVIII, FIX, FX and VWF activity occurs (7-9).Activities of FIII, FIX and VWF return to
normal within 4 hours after TPE, whereas the remaining coagulation factors achieve pre TPE levels by 24 hours (7).
The exception to this is fibrinogen, which reaches 66% of pre-apheresis levels by 72 hours (8). Theoretically, the
removal of inhibitors of coagulation could predispose patients to thrombosis, but this has not been demonstrated
definitively. (9-10). TPE may also remove medications. Although the effect of TPE on the majority of medications
is unknown due to limited pharmacokinetic studies, some drugs have been reported to have significant removal. (1112). Drugs that have been reported to be removed by the TPE are listed in table1.
It is important to realize that one third of the replacement fluid administered at the beginning of the PE will be
present by the end, with the majority having been removed. Administering plasma as a replacement fluid at the
beginning of a PE results in exposure of the patient to blood products without benefit.
The most commonly replacement fluid is 4%-5% human albumin in physiological saline. The solution has the
advantage of avoiding disease transmission and transfusion reactions (e.g. Transfusion related acute lung injury),
both of which can occur with plasma. The main disadvantage of albumin is its expense relative to plasma. This
replacement fluid is slightly hypertonic compared with plasma and may therefore expand intravascular volume. This
effect can be beneficial in avoiding hypovolemia. Because the albumin replacemt fluid is the most expensive
component of the TPE procedure and the use of 100% albumin as a replacement does expand intravascular, some
practitioners will use lower albumin concentrations, such as70% albumin and 30% saline. When this is done the, the
albumin and saline are alternated, with the majority of albumin being given at the end of the procedure to avoid
hypovolemia from redistribution of the crystalloid. It should be noted that the use of albumin and saline has been
associated with a greater frequency of hypovolemic reactions compared with using albumin alone (15). The removal
of antibodies from the patient can result in false negative tests for infectious diseases, autoantibodies, alloatibodies,
and enzyme and coagulation factor activity. Samples for
such testing should be collected before the initiation of TPE. Plasma is used as a replacement fluid in a limited
number of disorders, for example, to replace ADAMTS 13 when treating thrombotic thrombocytopenic purpura, to
treat coagulation factor deficiencies, and to prevent dilutional coagulopathy in patients with active bleeding (16).
Plasmapheresis is theoretically of greater value than hemodialysis or hemoperfusion in treating poisoning / overdose
by substances that are highly bound to proteins or lipids. The successful treatment of poisoning / overdose with
plasmapheresis has been reported for a number of agents. Protein bound toxins and drugs for which pheresis has
been reported useful include: methylparathion (organophosphate herbicide), Amanita phaloides (mushroom) toxin,
L-thyroxine, vincristine and cisplatin. (21). All of the reports evaluating treatment with plasmapheresis are case
reports or case series in which many of the patients were treated concurrently with dialysis and /or specific antidotes.
There has been no randomized controlled trial comparing plasmapheresis with other treatment modalities. Therefore,
recommendations for the treatment of poisoning and overdose are difficult. Plasmapheresis may be used in
exceptional cases or under a research protocol . Drugs and toxins for which plasmapheresishas been shown to
provide little or no benefit include: barbiturate, tricyclic antidepressants, benzodiazepines, quinine, phenytoin,
digoxin, prednisone, tobramycine and propanolol (21).
To perform TPE, it is necessary to obtain vascular access. The Canadian Apheresis study group found that 67% of
5234 TPE procedures could be completed successfully with peripheral venous access alone. (17)

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Complications of TPE:The frequency of complications associated with TPE reported in the literature is variable and is dependent upon
what is or what is not considered a reaction or an expected physiological response. Table 2 summarizes the reported
types of reactions and their frequencies in these patients. The reactions reported are, for the most part, mild and
easily treated. Risk factors for reactions include the use of plasma as are replacement fluid, (15,18,19) central
venous access (18,19) and the presence of neurological disease.(18)
To provide practical evidence based guidance to the apheresis, practitioner and to encourage crititical science in the
field of apheresis medicine, ASFA (American society of Apheresis) has published guide lines on the use of
therapeutic apheresis in clinical practice. The latest guidelines, published in 2010, are the fifth edition. (20).

Materials and methods:We retrospectively reviewed all the Plasmapheresis procedures performed over a period of 13 years, from August
2002 to july 2015 in the department of hematology at a tertiary care centre.
The indications for plasmapheresis were established by proper clinical and laboratory evaluation. Informed
consent was obtained from every patient prior to the procedure. ECG, Chest X ray, Serology for Hepatitis B and C,
HIV and blood grouping was done. The goal was to perform five exchanges on an alternate day schedule to reach a
therapeutic target of 150-200 ml of plasma removed per Kg of body weight.
We did Plasmapharesis on cell separator COBE spectra version 6.5(Fig.1) and all TPE procedures were completed
successfully with peripheral venous access alone. Cubital vein was mostly used for access and in only few patients
femoral vein was used as an access. All TPE procedures done were dual needle and replacement fluid used was
plasma. The procedure was continuous and automated and the anticoagulant used was ACD (activated citrate
dextrose).Patients were preloaded with 1.5-2 L of normal saline to get an adequate hydration status before the
procedure. The blood pump speed was set at of 60-80 ml/min . Blood pressure (BP) and pulse were monitored at
frequent intervals during the sessions and patients were closely observed for development of any complications and
overall status The initial part of PE was done with ringer lactate fluid replacement followed by fresh frozen plasma
in majority of patients as it is available free of cost at our centre. However, approximately 35 patients received
human albumin 20% as replacement fluid. Plasma associated infections were not reported in our unit as patient
would be shifted to respective department after completion of PE and could not maintain follow up with our unit.
The cost-effectiveness of plasmapheresis as a therapy varies greatly from disease to disease. For some diseases,
plasmapheresis is the only effective front- line therapy treatment, and it significantly improves patient quality of life.
For other diseases, plasmapheresis is only of limited utility and does not significantly improve patient quality of life.
There may also be alternative therapies available to treat certain diseases. In our center the cost per session of
plasmapheresis was approximately rupees 10,000 to 15,000 per session. However, those patients were plasma was
used instead of albumin, the cost per session was rupees 7,500.

Results:A total of 549 plasmaexchange(PE) procedures were performed on 105 patients. There were (68)male patients and
(37)female patients. Age ranged from 18 to 62 years . Age distribution of patients is given in the Table 3.
Various indications for plasmapharesis in our setup is given in Table 4.Most of our patients have been from
neurology and nephrology departments. Common indications have been Guillan Bare syndrome (31%),Myasthenia
Gravis (23%)Rapidly progressive glomerulonephritis (22%)
The target of our Plasmapheresis protocol was five exchanges in most of our patients, however some of the patients
could complete all the five sessions(Table 5) . Various reasons for incomplete PE sessions were significant
improvement after less number of exchanges (n = 5, ), significant hemodynamic instability during procedure (n =
1), and allergic reactions (n = 4).In some patients seven (15 cases)and six exchanges (5 cases) were also done.All
of these patients were more than five sessions of plasmapharesis were done were GBS on
ventilatorysupport,however 2 of these case died 2 weeks after last session and 1 patient died 1 month after last
session due to ventilator associated pneumonia.

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Average volume of plasma removed was 1.5 Liters per session.


Complications related to procedure are given in Table 6.Most common complication was paresthesias(36%)
followed by hypocalcemia(7%).
Table 1:- Medications reportedly removed by TPE.
Basiliximab
Ceftriaxone
Chloramphenicol
Verapam
IFN-
IVIG
Tobramycin
Propranolol
Propoxyphene
Cisplatin
Table 2:- Reactions due to TPE
Reaction
No of TPE procedures
Paresthesias
Urtricaria
Hypofibrinogenemia
Hypotension
Vasovagal reactions
Nausea
Others
Hemothorax
Catheter siteinfection
Bleeding/hematoma
Pneumothorax
Vomiting
NR indicates not reported

Ceftizidime
Diltiazim
Pavilizumab
Rituximab
Vincristine

Couriel and Weinstein (18)


381
5.5%
0.26%
3.67%
2.1%
0.5%
2.9%
0.5%
0.26%
0.26%
0.26%
0.26%
NR

Table 3:- Age distribution of patients.


Age group
<20 yrs
21-40
41-60
>60
Total
Table 4:- Indications for plasmapheresis.
Disease
GBS
MG
RPGNHUS/TTP
Myeloma
Renal graft rejection
Table 5:-Number of exchanges.
No. of exchanges
7
6
5
4
2
1
Total

(12,13,14,)

Basic-Jukic (19)
4857
2.7%
1.6%
NR
NR
NR
NR
NR
NR
0.04%
2.46%
0.06%

Basic-Jukic (19)
4857
2.7%
1.6%
NR
NR
NR
NR
NR
NR
0.04%
2.46%
0.06%

No.of cases
10
22
63
10
105

No. of patients
32
24
23
21
4
1

No.of patients
15
5
75
7
2
1
105

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International Journal of Advanced Research (2016), Volume 4, Issue 7, 859-864

Table 6:-Complications of plasmapheresis


Complications
Partesthesias
Hypocalcemia
Hypotension
Hypothermia
Urticaria

No.ofpatients(%)
36%
7%
3%
2%
1%

Fig.1:-Cobe spectra at our center

Discussion:-

First plasma pharesis was done on 30th august 2002. Till date 549plasmaexchanges have been done on 105 patients.
Most of our patients have been from neurology and nephrology departments. Common indications for the
procedure was Guillan Bare syndrome (31%) followed by Myasthenia Gravis (23%),Rapidly progressive
glomerulonephritis (22%),Haemolytic uremic syndrome, Thrombotic thrombocytopenic purpura (20%),Multiple
myeloma (4%)&Renal graft rejection (1%). According to the report of the therapeutics and technology assessment
subcommittee of the American Academy of Neurology on plasmapheresis in 2011, it was found that PE is extremely
safe in experienced hands.[16] .Majority of patients were adults in age range of 18-62 years.
The common reaction observed in our patients was Paresthesias (36%) attributed to the large fluid shifts between
the intra and extra vascular compartments with associated electrolyte imbalances and the citrate content of the
anticoagulant in the FFP .Few of our patients (7% ) developed hypocalcemia. Hypotension was seen in(3%) cases
which was managed by transiently stopping the procedure. Hypothermia was noted in 2% of patients. None of our
patients had procedure related nausea, vomiting, Vasovagal reactions, Pneumothorax, Hemothorax, bleeding,
hematoma, pruritis, tachycardia or fever. Urticaria was noted in 1% patients. We did not follow our patient for the
development of hypofibrinogenemia.

Conclusion:Plasmapheresis is safe, cost effective


mortality.

procedure with only minimal procedure related complications and no

Conflicts of interest:- None.

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